This major research program (MRP) is designed to study the effects of diabetes on pregnancy and the emphasis is to foster interdisciplinary collaboration involving basic science and clinical specialties. There are nine subprojects and these are described below: 1) The first project involves the kinetic studies of glucose using stable isotope to delineate the gluconeogenesis in normal and diabetic pregnant women. In this study, Dr. Cowett will also evaluate the neuro-control of carbohydrate metabolism in newborn lambs. 2) Using the chronic fetal hyperinsulinemia model, Dr. Susa will continue to evaluate the hormonal, metabolic, and peripheral tissue adjustment to this condition. 3) Allowing the chronic hyperinsulinemic fetus to deliver spontaneously, Dr. Schrier will study the behavioral changes of the newborn as well as infant monkeys. 4) Utilizing rat as the animal model, Dr. Oh will induce macrosomia and growth retardation by maternal diabetes and placental insufficiency respectively, lipogenesis at birth and during the first two months will be studied under various dietary intake with reference to lipogenesis. 5) Dr. Schwartz will continue his study on the HbAIC focusing on the glycosylation of fetal hemoglobin, the production of erythropoietin in the hyperinsulinemic fetus and its effect on fetal oxygenation. 6) In conjunction with Dr. Schwartz, Drs. Park and Agarwal will study the glycosylation of enzyme of purine metabolism in erythrocytes and the biochemical properties of the platelets i the diabetic pregnant woman. 7) Utilizing chronic hyperinsulinemia in sheep, Dr. Jackson will study the catecholamine secretion rate in the lamb fetus. 8) Using the same model, Dr. Stonestreet will study the circulatory changes and 9) Utilizing the fat tissue from these chronic hyperinsulinemic lamb fetuses, Dr. Fain will study the carbohydrate and lipid metabolism in adipocytes with specific reference to the effect of insulin and lipolytic hormones. All these subprojects will be coordinated both administratively and scientifically by a Core unit which will also continue to follow the children of diabetic mothers who were enrolled during the first five years of this MRP. The core program will also evaluate the HbAIC as a marker for the control of the diabetes during pregnancy.